Serum angiopoietin-2 and soluble VEGF receptor 2 are surrogate markers for plasma leakage in patients with acute dengue virus infection

Weg, Cornelia A. M. van de; Pannuti, Cláudio Sérgio; Ham, Henk-Jan van den; Araújo, Evaldo Stanislau Affonso de; Boas, Lucy S. Vilas; Félix, Alvina Clara; Carvalho, Karina I.; Levi, José Eduardo; Romano, Camila Malta; Centrone, Cristiane C.; Rodrigues, Célia Luiza de Lima; Luna, Expedito José de Albuquerque; Gorp, Eric C. M. Van; Osterhaus, Albert D. M. E.; Kallas, Esper G.; Martina, Benedict

doi:10.1016/j.jcv.2014.05.001

Cited by 48 publications

(26 citation statements)

References 46 publications

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“…MMP levels were highest after infection with the most virulent strain, D2-16681, followed by the prototype NGC strain in both cell lines. Our in vitro results support previous clinical findings that MMP-9 is associated with disease severity in dengue fever (3) and that increased MMP-2 levels are significantly associated with plasma leakage in DHF patients (20). In vitro studies have demonstrated that MMP overproduction as a result of dengue virus infections in endothelial cells or DCs can lead to increased cell permeability (5,15).…”

Section: Discussionsupporting

confidence: 89%

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Relationship between MMP Expression and Virulence of Dengue Virus Type-2 in Infected Mosquito and Mammalian Cells

et al. 2016

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SUMMARY:Dengue virus infections are mostly asymptomatic but can produce a mild, self-limiting acute febrile illness, dengue fever, or a life threatening severe illness, dengue hemorrhagic fever. Dengue hemorrhagic fever is associated with increased vascular permeability partly as a result of elevated levels of matrix metalloproteinases (MMPs). We characterized MMP-2 and MMP-9 production in mosquito and mammalian cells after infection with three strains of dengue virus type-2 (D2-) ranging in virulence: 16681, the prototype New Guinea C (NGC), and PDK-53 vaccine strain. These strains were used to test variations in viral properties in vaccine candidates and confirm the production of MMP as a possible marker for virulence. A zymogram gelatinolytic activity assay was used to assess MMP-2 and MMP-9 production. We found that dengue-infected mosquito and mammalian cell lines had unique MMP-2 and MMP-9 production patterns depending on the virulence of the infecting dengue strain and the duration infection. MMP levels were highest after infection with the most virulent strain D2-16681, followed by the prototype NGC strain, in both cell lines. The MMP levels appeared to correspond with the relative amounts of infectious virions produced later in infection. Our findings improve our understanding of dengue pathogenesis and may facilitate the selection of markers to further the development of dengue vaccines.

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Section: Discussionsupporting

confidence: 89%

“…Others have suggested that MMPs may be used as a biological marker of dengue infection severity because MMP levels correlate with the pathogenesis of dengue virus infections and plasma leakage (15,20). Thus, MMP levels in recipients of candidate dengue vaccines may be important markers to consider.…”

Section: Discussionmentioning

confidence: 99%

Relationship between MMP Expression and Virulence of Dengue Virus Type-2 in Infected Mosquito and Mammalian Cells

et al. 2016

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“…53 Over-275 expression of sFlt-1 and sEng leads to increased microvascular with reports of sEng as a vascular permeability factor, but conflict 284 with a recent study that found no difference in circulating sEng 285 levels in dengue patients with plasma leakage assessed by X-ray or 286 ultrasound on admission. 58 It is also possible that sEng may be 287 modulating inflammatory responses through its effects on TGF-b 288 signalling. 289…”

mentioning

confidence: 99%

Host biomarkers are associated with progression to dengue haemorrhagic fever: a nested case-control study

Conroy

Gélvez

Hawkes

et al. 2015

International Journal of Infectious Diseases

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“…However, VEGF is elevated in dengue with warning signs/ severe dengue [26], but care must be taken when comparing with studies conducted in children [27][28][29].…”

Section: Discussionmentioning

confidence: 99%

Biomarkers in differentiating clinical dengue cases: A prospective cohort study

Kim¹,

Low²,

Gan³

et al. 2015

J Coast Life Med

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Serum angiopoietin-2 and soluble VEGF receptor 2 are surrogate markers for plasma leakage in patients with acute dengue virus infection

Abstract: Angiopoietin-2 and soluble VEGFR-2 can serve as surrogate markers for the occurrence of plasma leakage in patients with acute DENV infection.

Cited by 48 publications

References 46 publications

Relationship between MMP Expression and Virulence of Dengue Virus Type-2 in Infected Mosquito and Mammalian Cells

Relationship between MMP Expression and Virulence of Dengue Virus Type-2 in Infected Mosquito and Mammalian Cells

Host biomarkers are associated with progression to dengue haemorrhagic fever: a nested case-control study

Biomarkers in differentiating clinical dengue cases: A prospective cohort study

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